Macrolide antibiotics decrease neutrophils and IL-8 concentration in BAL of subjects with DPB- and sputum IL-8 concentration in CF. Macrolides can inhibit IL-8 release from airway epithelial cells in culture through inactivation of ERK or NK-kB.
Dapsone, a synthetic sulfone, has been used to treat leprosy, Pneumocystis jiroveci pneumonia, and malaria. Dapsone also is recognized as an antiinflammatory drug and has been used systemically and topically to treat skin diseases like dermatitis herpetiformis, which is characterized by neutrophil-dominated inflammation. We speculated that dapsone would inhibit IL-8 secretion by stimulated airway cells; therefore, we studied the effect of dap-sone on IL-8 secretion from NHBE cells stimulated with LPS and further investigated the signaling pathways involved. We then evaluated the effectiveness of dapsone in decreasing airway neutrophil recruitment and preserving mucociliary clearance when administered orally or as an aerosol to ferrets with airways that had been exposed to (ie, inflamed by) LPS.
Materials and Methods Cheap tadalafil Canada
Dapsone (4,4′-diaminodiphenyl sulfone), LPS (Escherichia coli serotype 0111:B4), and all other reagents were purchased from Sigma-Aldrich Corp (St Louis, Missouri), unless otherwise indicated. PD98059 (2 – -amino-3′-methoxyflavone), an MAPK/ERK kinase (MEK) inhibitor (an upstream kinase of ERK1/2) was obtained from Calbiochem (La Jolla, California). Phospho- and nonphospho-specific ERK1/2, anti-p38 MAPK, anti-stress-activated protein kinase (SAPK)/JNK, and phospho-specific NF-kB p65 (Ser536) as well as anti-rabbit-IgG horseradish peroxidase (HRP) antibodies were purchased from Cell Signaling Technology, Inc (Beverly, Massachusetts). Dimethylsulfoxide (DMSO) was used as a solvent of dapsone, and the final concentration did not exceed 0.01% (v/v). Preliminary in vitro experiments showed that 0.01% DMSO medium had no significant effect on cell viability and IL-8 secretion for up to 72 h (data not shown).